Zimberelimab and Domvanalimab in Combination With Chemotherapy Versus Pembrolizumab With Chemotherapy in Patients With Untreated Metastatic Non-Small Cell Lung Cancer (STAR-121)

• ClinicalTrials.gov Identifier: NCT05502237
• Recruitment Status: Recruiting
• First Posted: August 16, 2022
• Last Update Posted: May 1, 2024
• Sponsor: Gilead Sciences
• Collaborator: Arcus Biosciences, Inc.
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: August 12, 2022
• First Posted Date: August 16, 2022
• Last Update Posted Date: May 1, 2024
• Actual Study Start Date: October 12, 2022
• Estimated Primary Completion Date: September 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 12, 2022)

• Progression-free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 [ Time Frame: Up to 31 months ]
  PFS is defined as the time from the date of randomization until disease progression (PD) or death from any cause, whichever comes first.
• Overall Survival (OS) [ Time Frame: Up to 58 months ]
  OS is defined as the time from the date of randomization to the date of death from any cause.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 12, 2022)

• Objective Response Rate (ORR) as Assessed by BICR per RECIST Version 1.1 [ Time Frame: Up to 58 Months ]
  ORR is defined as the proportion of participants who have achieved a complete response (CR) or partial response (PR) that is confirmed at least 4 weeks later.
• Duration of Response (DOR) as Assessed by BICR per RECIST Version 1.1 [ Time Frame: Up to 58 Months ]
  DOR is defined as the time from the first response (CR or PR), to the first documented PD or death from any cause, whichever comes first.
• Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) [ Time Frame: First dose date up to 58 months plus 30 days ]
• Percentage of Participants Experiencing Clinical Laboratory Abnormalities [ Time Frame: First dose date up to 58 months plus 30 days ]
• Time to First Symptom Deterioration in Non-small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) Total Score [ Time Frame: Baseline, Up to 58 Months ]
  The NSCLC-SAQ is a patient reported outcome measure with seven items assessing five symptom concepts of NSCLC: cough, pain, dyspnea, fatigue, and appetite. Each item is rated using a five-point verbal rating scale from "No <symptom> At All" to "Very severe <symptom>" or from "Never to Always," corresponding to a score of 0 to 4. The sum of all 5 domain scores will be computed, if any scores are missing, a total score will not be computed. The total score ranges between 0 and 20 with higher scores indicating more severe symptoms.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Zimberelimab and Domvanalimab in Combination With Chemotherapy Versus Pembrolizumab With Chemotherapy in Patients With Untreated Metastatic Non-Small Cell Lung Cancer
• Official Title: A Randomized, Open-Label, Phase 3 Study to Evaluate Zimberelimab and Domvanalimab in Combination With Chemotherapy Versus Pembrolizumab With Chemotherapy for the First-Line Treatment of Patients With Metastatic Non-Small Cell Lung Cancer With No Epidermal Growth Factor Receptor or Anaplastic Lymphoma Kinase Genomic Tumor Aberrations
• Brief Summary: The primary objective of this study is to compare the effect of zimberelimab (ZIM) and domvanalimab (DOM) in combination with chemotherapy relative to pembrolizumab (PEMBRO) in combination with chemotherapy on progression-free survival (PFS) and overall survival (OS) in patients with untreated metastatic non-small cell lung cancer with no actionable genomic alteration.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-small Cell Lung Cancer

Intervention

• Drug: Zimberelimab
  Administered intravenously
  Other Names:

  • GS-0122
  • AB122
• Drug: Domvanalimab
  Administered intravenously
  Other Names:

  • GS-0154
  • AB154
• Drug: Pembrolizumab
  Administered intravenously
  Other Name: KEYTRUDA®
• Drug: Carboplatin
  Administered intravenously
• Drug: Cisplatin
  Administered intravenously
• Drug: Paclitaxel
  Administered intravenously
• Drug: Nab-paclitaxel
  Administered intravenously
• Drug: Pemetrexed
  Administered intravenously

Study Arms

• Experimental: Zimberelimab (ZIM) +Domvanalimab (DOM) + Chemotherapy

  Participants will receive ZIM 360 mg + DOM 1200 mg (up to 35 doses) with chemotherapy every 3 weeks (Q3W) on Day 1 of each 21-day cycle.

  Choice of chemotherapy is dependent on histology.

  • Participants with nonsquamous histology will receive cisplatin 75 mg/m^2 or carboplatin area under the concentration versus time curve (AUC)5 + pemetrexed 500 mg/m^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m^2 Q3W until disease progression or intolerable toxicities.
  • Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m^2 Q3W or nab-paclitaxel 100 mg/m^2 weekly (QW) for first 4 cycles.
  Interventions:

  • Drug: Zimberelimab
  • Drug: Domvanalimab
  • Drug: Carboplatin
  • Drug: Cisplatin
  • Drug: Paclitaxel
  • Drug: Nab-paclitaxel
  • Drug: Pemetrexed
• Active Comparator: Pembrolizumab (PEMBRO) + Chemotherapy

  Participants will receive PEMBRO 200 mg (up to 35 doses) with chemotherapy Q3W on Day 1 of each 21-day cycle.

  Choice of chemotherapy is dependent on histology.

  • Participants with nonsquamous histology will receive cisplatin 75 mg/m^2 or carboplatin AUC 5 + pemetrexed 500 mg/m^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m^2 Q3W until disease progression or intolerable toxicities.
  • Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m^2 Q3W or nab-paclitaxel 100 mg/m^2 weekly (QW) for first 4 cycles.
  Interventions:

  • Drug: Pembrolizumab
  • Drug: Carboplatin
  • Drug: Cisplatin
  • Drug: Paclitaxel
  • Drug: Nab-paclitaxel
  • Drug: Pemetrexed
• Experimental: Zimberelimab (ZIM) + Chemotherapy

  Participants will receive ZIM 360 mg (up to 35 doses) with chemotherapy Q3W on Day 1 of each 21-day cycle.

  Choice of chemotherapy is dependent on histology.

  • Participants with nonsquamous histology will receive cisplatin 75 mg/m^2 or carboplatin AUC 5 + pemetrexed 500 mg/m^2 Q3W for first 4 cycles After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m^2 Q3W until disease progression or intolerable toxicities.
  • Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m^2 Q3W or nab-paclitaxel 100 mg/m^2 weekly (QW) for first 4 cycles.
  Interventions:

  • Drug: Zimberelimab
  • Drug: Carboplatin
  • Drug: Cisplatin
  • Drug: Paclitaxel
  • Drug: Nab-paclitaxel
  • Drug: Pemetrexed

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 12, 2022): 720
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 2027
• Estimated Primary Completion Date: September 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Life expectancy ≥ 3 months.

• Pathologically documented NSCLC that meets both of the criteria below:

  • Have documented evidence of Stage IV NSCLC disease at the time of enrollment (based on American Joint Committee on Cancer (AJCC), Eighth Edition).
  • Have documented negative test results for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations.
• Have no actionable genomic alterations such as ROS proto-oncogene 1 (ROS1), neurotrophic tyrosine receptor kinase (NTRK), proto-oncogene B-raf (BRAF), RET mutations, or other driver oncogenes with approved frontline therapies.
• Have not received prior systemic treatment for metastatic NSCLC.
• Measurable disease per RECIST v1.1 criteria by investigator assessment.
• Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1.
• Have adequate organ functions.

Key Exclusion Criteria:

• Have mixed small-cell lung cancer (SCLC) and NSCLC histology.
• Positive serum pregnancy test or individuals who are breastfeeding or have plans to breastfeed during the study period.
• Received prior treatment with any anti-PD-1, anti-PD-L1, or any other antibody targeting an immune checkpoint.
• Known hypersensitivity to the study drug, its metabolites, or formulation excipient.
• Have an active second malignancy or have had an active second malignancy within 3 years prior to enrollment.
• Have an active autoimmune disease that required systemic treatment in past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs).
• Are receiving chronic systemic steroids.
• Have significant third-space fluid retention.
• Have untreated central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or gastrointestinal perforation within 6 months of enrollment.
• Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Has had an allogenic tissue/solid organ transplant.
• Have received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu and COVID-19 vaccines that do not contain live virus are permitted.
• Have known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Gilead Clinical Study Information Center; 1-833-445-3230 (GILEAD-0); GileadClinicalTrials@gilead.com

• Listed Location Countries: Argentina, Austria, Belgium, Brazil, Canada, Chile, China, France, Germany, Hong Kong, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Portugal, Singapore, Spain, Taiwan, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT05502237
• Other Study ID Numbers: GS-US-626-6216; 2022-000578-25 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Gilead Sciences
• Original Responsible Party: Same as current
• Current Study Sponsor: Gilead Sciences
• Original Study Sponsor: Same as current
• Collaborators: Arcus Biosciences, Inc.

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

• PRS Account: Gilead Sciences
• Verification Date: April 2024